This proposal will test the long-term impact of the Family Check-Up (FCU) approach to preventing substance use and other high-risk problem behaviors from toddlerhood through adolescence by enhancing parenting. A critical question for a randomized prevention trial such as this is the extent to which early family support reduces adolescent alcohol and drug use (ADU), high-risk sexual behavior linked to HIV-AIDS, and serious problem behaviors in adolescence. The study also will examine how reduction in these adolescent problem behaviors is mediated by improvement in parenting and peer environments and is moderated by the family ecology and genetic risk. The proposed study will include follow-up assessments of 731 children through adolescence that include the collection of DNA; observations of family interaction; parent, youth and teacher report of adjustment; and assessments of and reports about peer environments. The Early Steps (ES) multisite sample was recruited from WIC centers in three geographically, socioeconomically, and ethnically diverse communities: Pittsburgh, PA; Charlottesville, VA; and Eugene, OR. To increase the number of sample families at risk for later ADU, eligibility was restricted to WIC families with additional socioeconomic (i.e., low parental education), family (i.e., maternal stress), and child (i.e., toddler conduct problems) risk factors. The children and families were initially assessed at child age 2 and then yearly through age 10.5, using a multi-agent and multi-method strategy that included direct observations of family interaction in most years. Families were randomly assigned to be offered a yearly FCU intervention, including adapted and tailored family management interventions. Specifically, the Family Check-Up will be evaluated as it relates to reducing adolescent substance use, high-risk sexual behavior linked to HIV, and other serious problem behavior at ages 14 and 16, how such intervention effects might be mediated by changes in parenting, and moderated by neighborhood adversity and GxE interactions.